Clinical Trials Register

Summary
EudraCT Number:	2006-000658-27
Sponsor's Protocol Code Number:	D5130C05262
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2006-12-19
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2006-000658-27

A.3

Full title of the trial

A Randomised, Double-blind, Parallel Group, Phase 3, Efficacy and Safety Study of AZD6140 Compared with Clopidogrel for Prevention of Vascular Events in Patients with Non-ST or ST Elevation Acute Coronary Syndromes (ACS)[PLATO – A Study of PLATelet inhibition and Patient Outcomes]

A.3.2

Name or abbreviated title of the trial where available

PLATO

A.4.1

Sponsor's protocol code number

D5130C05262

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AstraZeneca AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	AZD6140 90 mg
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ticagrelor
D.3.9.1	CAS number	274693-27-5
D.3.9.2	Current sponsor code	AZD6140
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	90
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Plavix 75 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Pharma Bristol-Myers Squibb SNC
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	clopidogrel
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	clopidogrel
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	75
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

non-ST and ST elevation acute coronary syndromes (ACS)

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	8.1
E.1.2	Level	HLT
E.1.2	Classification code	10011085
E.1.2	Term	Ischaemic coronary artery disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to test that AZD6410 is superior to clopidogrel for prevention of vascular events (death from vascular causes, MI, stroke) in patients with non-ST or ST elevation acute coronary syndromes (ACS).

E.2.2

Secondary objectives of the trial

- To assess the safety and tolerability of AZD6140 compared to clopidogrel.
- To assess the efficacy and safety of AZD6140 and clopidogrel in those patients
undergoing coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) during the study.
- To assess the occurrence of arrhythmic episodes detected by Holter monitoring during the initial period after randomization and at one month.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

ECG substudy (same date as main study protocol)
Objectives: To assess whether ST-T changes at hospital entry modulate AZD6410 treatment effect. To analyse whether ST changes in combination with biomarkers improve patient risk stratification over biomarkers alone. To assess differences between AZD6410 and clopidogrel treatment on ECG patterns at hospital discharge.

Blood core substudy (same date as main study protocol)
Objectives: To follow biomarkers over time and identify differences between AZD6410 and clopidogrel treated groups. To find correlations between clinical outcomes in these groups and biomarker levels at hospital entry, and at discharge or at one month. To assess the influence of the genetic constitution of AZD6140 treated patients on clinical outcomes and biomarker levels. To employ integrated proteomic and metabolomic and cellular analyses as candidate and discovery biomarkers for predicting clinical outcomes and drug safety. To investigate whether advanced biomarkers can predict drug safety and efficacy. To determine the prognostic value of advanced biomarkers.

Angiography substudy (same date as main study protocol)
Objective: investigate if the use of AZD6140 will be associated with further improvements in flow and perfusion on coronary angiography in the setting of ACS.

Health economics and quality of life substudy (same date as main study protocol)
Objectives: to estimate the incremental cost effectiveness ratio of AZD6410 compared to clopidogrel in patients with ACS.

Genetic research (same date as main study protocol)
Objectives: To obtain DNA samples for future exploratory research on the effects of genetic polymorphisms on i) the response to AZD6410 and clopidogrel, ii) the disposition of AZD6410 and clopidogrel and iii) the susceptibility to and prognosis of ACS under study

E.3

Principal inclusion criteria

1. Index event of non-ST or ST segment elevation ACS. The patient should be hospitalised for chest pain and potential ACS and the onset of the most recent cardiac ischaemic symptoms of the index event must occur within the 24 hours before randomisation and be documented by cardiac ischaemic symptoms of ≥10 minutes duration at rest AND (i, ii, or iii):

i) Persistent ST segment elevation ≥1mm (0.1 mV) in 2 or more contiguous leads and primary PCI planned
OR
ii) New or presumed new left bundle branch block (LBBB) and primary PCI planned
OR
iii) Cardiac ischaemic symptoms of ≥10 minutes duration at rest and at least 2 of the following 3 criteria (A-C):

A) ST segment changes on ECG indicative of ischaemia
B) Positive biomarker (Troponin I or -T or CK-MB) evidence of myocardial necrosis
C) Having at least one of the following risk factors: Aged 60 or over, Previous MI or CABG, Known multi-vessel coronary artery disease (CAD), Previous ischaemic stroke, TIA, carotid stenosis, or cerebral revascularisation, Diabetes mellitus, Peripheral arterial disease, Chronic renal dysfunction

2. Provision of signed informed consent form.
3. Male or female aged at least 18 years
4. Females of child-bearing potential who are willing to use 2 methods of contraception.

E.4

Principal exclusion criteria

1. Contraindication or other reason that clopidogrel or AZD6140 should not be administered.
2. Index event is a complication of PCI
3. Patient has undergone PCI after the index event and before the first dose of study treatment
4. Oral anticoagulation therapy that cannot be stopped
5. Fibrinolytic therapy in the 24 hours prior to randomisation, or planned fibrinolytic
treatment following randomisation
6. Increased risk of bradycardic events
7. Patient requires dialysis
8. Platelet count less than 100 x 10E9/L
9. Haemoglobin (Hb) level less than 100 g/L
10. Participation in another investigational drug or device study in the last 30 days
11. Pregnancy or lactation
12. Concomitant oral or intravenous therapy with strong CYP 3A inhibitors, CYP3A substrates with narrow therapeutic indices, or strong CYP3A inducers which cannot be stopped for the course of the study
13. Any other condition which in the opinion of the investigator, may either put the patient at risk or influence the result of the study
14. Involvement in the planning and conduct of the study
15. Previous enrolment or randomisation of treatment in the present study.

E.5 End points

E.5.1

Primary end point(s)

Time to the first occurrence of any event from the composite of death from vascular causes(*), myocardial infarction and stroke.
(*): Death from vascular causes includes CV deaths, cerebrovascular deaths, and any other death for which there was no clearly documented non-vascular cause.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Quality of Life - Patient reported outcomes

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

double dummy

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

1000

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

End of study is defined as date of database lock which is the timepoint after which no patient will be exposed to study-related activities.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	Yes
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	650
F.4.2	For a multinational trial
F.4.2.1	In the EEA	10000
F.4.2.2	In the whole clinical trial	18000

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2006-11-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2006-10-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2009-04-20

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials